The long-term goal of this research project is to produce neurophysiological data that will lead to a deeper understanding of the operation of the human oculomotor system. The results produced by this project should also have diagnostic value for a number of human neurological disorders with oculomotor manifestations. Further they should aid in the understanding of the cause of several oculomotor disorders that severely limit visual function. Among oculomotor systems the saccadic system occupies a preeminent position as a model system for increasing the understanding of internally controlled movements in general. The research proposed for the next project period is designed to investigate the operation of neural circuitry participating in saccade generation in a broad range of neural structures from the frontal cortex and superior colliculus, through the cerebellum and its brainstem connections. There are three specific aims: 1) The hypothesis that neural circuits intrinsic to the superior colliculus (SC) provide trajectory guidance throughout the entire saccadic eye movement rather than just initial directional specification will be tested. This goal will be achieved by studying neural activity at critical sites in the SC associated with the curved saccades produced in a simple visual search paradigm. Microstimulation at similar sites in the SC or the cortical frontal eye field (FEF) utilizing a novel stimulation waveform that mimics the expected neural activity will be used to determine causality. 2) The role of the nucleus reticularis tegmenti pontis (NRTP) and its loop connections to the caudal fastigial nucleus (cFN) in the cerebellum in the control of saccadic eye movements will be determined. Neural discharge will be sampled throughout the NRTP during saccades and the library of responses produced will be used with a previously developed algorithm to search for topographically organized spatiotemporal activity specifying the saccade goal. Reversible chemical lesions will be placed in NRTP and the presence of field deficits following the lesions will be investigated. The information fed back to the NRTP from the cFN will be investigated with electrophysiological techniques in NRTP and cFN. 3) The hypothesis will be tested that neurons in the FEF which show a sustained visual response in a delayed saccade paradigm also retain a memory of the original saccadic goal during interrupted saccades. These cells then play a role in guiding the resumed movement to the original target following the perturbation.